PET tracer measures damage in mouse model MS

January 19, 2018

There is currently no reliable way to get a direct image of demyelination. Physicians rely on MRI. Despite high resolution images, MRI is not quantitative and cannot distinguish between demyelination and inflammation, which often coexist in people with MS. But a novel approach may improve diagnosis and monitoring for MS patients.

A multi-institutional team based at the University of Chicago Medicine and the National Institutes of Health has conducted early tests of a novel minimally-invasive way to assess myelin damage using positron emission tomography. These PET scans use a radioactive molecule designed to target voltage-gated potassium channels, a protein found on demyelinated axons. The PET images, based on the detection of this molecule, provide quantitative information about underlying biochemical processes. Exposed neurons leak intracellular potassium. This leaves them unable to propagate electrical impulses, which causes some of the neurological symptoms seen in MS. The researchers developed a PET tracer that can target potassium channels.

The team started with an existing MS drug, 4-aminopyridine (a.k.a. dalfampridine), which can bind to exposed potassium channels. This can partially restore nerve conduction and alleviate neurological symptoms in MS patients. Using mouse models of MS, the researchers showed that the drug accumulated in the demyelinated areas of the central nervous system.

Then the team examined several fluorine-containing derivatives of 4-aminopyridine for binding to K+ channels. They found that 3-fluoro-4-aminopyridine has the desired properties, so they labeled the molecule with fluorine-18, which is easily detected by PET. The team was able to show, in rats, that the tracer accumulated to a higher degree in demyelinated areas than in control areas.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers conducted a study in healthy monkeys. They confirmed that radiolabeled 3F4AP enters the brain of primates and localizes to areas where there is little myelin.